Parkinson's Disease (PD) is worldwide the second most-common neurodegenerative disorder. Its diagnosis is based on clinically observable “cardinal” motor symptoms that are attributed to the loss of dopamine-producing nerve cells in one area of the brain. Dopamine is the critical neuropharmacological facilitator between nerve cells affected in PD. However, by the time cardinal motor symptoms appear, over 60% of the neurons are lost thus complicating interventional strategies as the disease process is rather advanced. Early markers or identification of at-risk patients would vastly improve therapeutic outcomes for neuroprotective types of therapy.
The eye is a window to the brain. Many processes which affect the brain also affect the back of the eye. Optical Coherence Tomography (OCT) is a commercially available diagnostic equipment that is widely used by ophthalmologists and optometrists. OCT is an optical signal acquisition and processing method that has been used in the study of ocular physiology and pathology since 1991. OCT allows imaging of the back of the eye and measuring with great precision changes in its nerve cells. The technique takes little time, typically five minutes, is non-invasive and the equipment is available in many doctors' offices. The test yields imaging and quantification of the thickness of the retina of the eye. The resolution of in-vivo retinal imaging using OCT is around five microns. This resolution is not sufficient to distinguish different cell types of the retina.
Over the last decades it has become apparent that non-motor systems, including vision, are affected by PD, with the retina being one site of pathology. PD apparently selectively affects certain retinal nerve layers and there is a remodeling of the retina in PD. The effects of PD in the human retina are consistent with results obtained in experimental models in monkeys and rodents. Impaired retinal processing in PD and in the monkey model of PD were originally shown by electroretinographic (ERG) recordings. The pattern ERG is determined by retinal ganglion cell activity and predominantly reflects foveal visual processing, which normally mediates optimum contrast and color vision. However, the ERG is not ideal to serve as a clinical large scale diagnostic tool.
The remodeling and pathology of PD can be quantified using OCT. For the differential diagnosis of PD and for potential follow-up of patients undergoing therapy with so-called neuroprotective drugs, the OCT may be a tool: non-invasive, widely available and relatively inexpensive. OCT has been used in neurology research to look at the thinning of the surface of the retina in Multiple Sclerosis and related demyelinating disorders. These layers can be seen on fundoscopy, a routine ophthalmological procedure. In recent years electroretinographic evidence of fovealdysfuncion of the retina in PD was supported by OCT. This can be used to form three-dimensional images from within any optical scattering medium. The currently used spectral-domain OCT (SD-CT) achieves micrometer-resolution and can be used to visualize different layers of the multilayered neural tissue of the retina. Thinning of the most superficial, inner layer, the so-called nerve fiber layer (NFL), was first reported in PD 2004. Several subsequent studies corroborated that the NFL is thinned in PD. These data raised some hopes that OCT may be useful as a biomarker for PD. However there are hurdles in the way of adopting OCT for multicenter large scale biomarker studies.
One problem is that there are differences in the quantification programs developed by the three major OCT equipment manufacturers. As a result, retinal thickness data are not simply transferable. The two most widely used equipments, RT-VUe and Zeiss Cirrus have different sampling rates and yield different thickness values for the same eye.
Another problem is that OCT, as almost every imaging technique, yields masses of data and it is unclear what measures and what thickness of the retina one should compare across equipments.
In addition, OCT thickness measurements are either based on the manufacturers' automated programs or manual measurements. Automated programs are geared to the diagnosis of glaucoma or maculopathy, neither of these programs are specifically suited to PD. Manual measurements not only require many repeats but also entail variability and vagaries due to reference line fitting and distortions introduced by the equipment's software for imaging.
Neurologists currently do not use OCT as a diagnostic tool for PD because there is no methodology to quantify the layers below the ganglion cells. Hence there is no technique to evaluate a patient for PD or other neurological disorders using data and/or information obtained from OCT.